Heat stress suppresses MnSOD expression via p53-Sp1 interaction and induces oxidative stress damage in endothelial cells: Protective effects of MitoQ10 and Pifithrin-α.

Aim: To investigate the mechanism of p53-mediated suppression of heat stress-induced oxidative stress damage by manganese superoxide dismutase (MnSOD) in endothelial cells (ECs). Methods: Primary ECs isolated from mouse aortas were used to examine the effects of heat stress on vascular ECs viability and apoptosis. We measured MnSOD expression, reactive oxygen species (ROS) production, p53 expression, viability, and apoptosis of heat stress-induced ECs. We also tested the protective effects of MitoQ10, a mitochondrial-targeted antioxidant, and Pifithrin-α, a p53 inhibitor, in ECs from a mouse model of heat stroke. Results: Heat stress increased cellular apoptosis, ROS production, and p53 expression, while reducing cellular viability and MnSOD expression in ECs. We also showed that the suppression of MnSOD expression by heat stress in ECs was mediated by interactions between p53 and Sp1. Furthermore, MitoQ10 and Pifithrin-α alleviated heat stress-induced oxidative stress and apoptosis in ECs. Conclusion: Our results revealed that p53-mediated MnSOD downregulation is a key mechanism for heat stress-induced oxidative stress damage in ECs and indicated that MitoQ10 and Pifithrin-α could be potential therapeutic agents for heat stroke.

Extracellular superoxide dismutase, a potential extracellular biomarker candidate for prolactinoma / Superóxido dismutasa extracelular - candidato potencial a biomarcador extracelular del prolactinoma

AIM: To investigate whether the extracellular superoxide dismutase (EC-SOD) and manganese super-oxide dismutase (Mn-SOD) level changes during prolactinoma (PRL) development. METHODS: Surgical tissues from 37 female patients with PRL were tested for Mn-SOD and serum samples from such PRL patients were tested for EC-SOD level changes with Western Blot. The Mn-SOD level from blood cells was also investigated to show whether the Mn-SOD variation could locate tumorigenesis tissues. RESULTS: According to the patients' age analysis, age 20-40 years is high risk for getting PRL. There is a positive relationship between the PRL severity and EC-SOD. The Mn-SOD level from surgical tissues, but not blood cells, also shows a corresponding positive relationship to PRL severity, which indicates that elevated Mn-SOD might only happen in PRL tumorigenesis tissues. CONCLUSIONS: Extracellular superoxide dismutase is an extracellular protein and the serum EC-SOD could be a good candidate for the diagnoses of prolactinoma.

OBJETIVO: Investigar los cambios de niveles del superóxido dismutasa extracelular (EC-SOD) y el superóxido dismutasa de manganeso (Mn-SOD) durante el desarrollo del prolactinoma (PRL). MÉTODOS: Los tejidos quirúrgicos de 37 pacientes hembras con PRL fueron examinados para investigar los niveles de cambio de Mn-SOD, mediante la técnica de Western Blot. El nivel de Mn-SOD de las células sanguíneas fue investigado para ver si la variación de Mn-SOD puede indicar la localización de tejidos de tumorigénesis. RESULTADOS: Según el análisis de la edad de los pacientes, la edad de 20-40 años presenta un alto riesgo de desarrollar PRL. Hay una relación positiva entre la severidad del PRL y el EC-SOD. El nivel de Mn-SOD en los tejidos quirúrgicos - a diferencia de lo que ocurre en las células sanguíneas - muestra una relación positiva con respecto a la severidad del PRL, lo cual indica que un Mn-SOD elevado, sólo podría tener lugar en los tejidos de la tumorigénesis del PRL. CONCLUSIONES: El superóxido dismutasa extracelular (EC-SOD) es una proteína extracelular, y el EC-SOD sérico podría ser un buen candidato para diagnosticar el prolactinoma.